The goals of this study have been 1) to develop a new large animal model of experimental hypertension and 2) to define the sequence of changes that lead from the intervention used to initiate the hypertension to the vascular changes responsible for the increase in total peripheral resistance. Models of renal and DOCA hypertension have been developed in the pig and we are now monitoring numerous parameters which we consider to be relevant to the pathogenesis of hypertension. These include: 1) hemodynamic changes (arterial and venous central pressures, cardiac output and total peripheral resistance), 2) water and electrolyte balances and body fluid volumes (plasma, extracellular and total body water), 3) renal function, 4) endocrine levels (desoxy-corticosterone, aldosterone, renin, and prostaglandin), 5) vascular reactivity (a) whole body response to norepinephrine or to angiotensin, (b) vascular resistance and reactivity of perfused hind legs one of which has been protected from the hypertension by common iliac artery ligation, 6) Windkessel compliance, 7) venous compliance, 8) autoregulatory response to volume loading, 9) vascular smooth muscle reactivity, 10) calcium uptake and efflux from microsomal and mitochondrial fractions of vascular smooth muscle. BIBLIOGRAPHIC REFERENCES: Hansen, T.R. and D.F. Bohr: Hypertension, transmural pressure, and vascular smooth muscle response in rats. Circ. Res. 36:590-598, 1975. Greenberg, S. and D.F. Bohr: Venous smooth muscle in hypertension. Cric. Res. 36 & 37, Suppl. I, 208-215, 1975.